Skeletal Muscle Plasticity As An Indicator of Functional Performance Post-Stroke

描述（由申请人提供）： 与中风后轻偏瘫相关的主要损害是在有目的的复杂协同作用（例如，行走时的协调）。毫不奇怪，中风对行走的影响是 重要的是，不到50%的幸存者进入独立的社区援助。即使在那些实现独立截肢的患者中，平衡和步态速度仍存在显著的残余缺陷，约75%的卒中后患者报告与行走相关的活动受限。肌无力是生活在美国的近600万中风幸存者中最突出的运动后果，也是这个大型临床队列中功能障碍的最强预测因素。到目前为止，导致偏瘫患者肌肉功能障碍的生理机制在很大程度上尚未研究。此外，有关旨在减轻中风后人群中受损肌肉功能的干预措施的疗效和随后的功能后果的证据是不明确的，并且补救轻偏瘫肌无力的可行治疗选择仍然是生物医学研究最紧迫的挑战之一。我们认为，受损的肌肉力量（肌肉力量和速度的产品）的产生是中风后功能（行走）残疾的原因。此外，协调缺陷也是功能表现的关键决定因素。我们已经开发了一个全面的理论框架，定义和测量肌肉功能和协调障碍的潜在因素，并将此框架应用于使用爆发性阻力（POWER）训练的中风后步行优化。我们在四年资助期内的目标是：1）量化导致中风后肌肉发电受损的神经和肌肉适应; 2）评估POWER训练对轻瘫和非轻瘫肌肉神经和肌肉适应的影响; 3）确定POWER训练后神经和肌肉适应变化与运动改善之间的关系。拟议工作的创新方面包括新颖的训练干预;先进的磁共振评估;以及我们提出的协调的独特措施。我们认为：a）中风后的神经和肌肉适应与受损的肌肉发电以及运动能力相关，B）POWER训练通过解决潜在的神经和肌肉元素来减轻功能缺陷，以及c）训练后的功能改善基于改善肌肉发电的最突出的神经和肌肉贡献者。如果正确的话，所产生的数据将提供一个全新的证据水平，证明这种新的干预策略对改善功能表现的有效性，以及外周肌肉特性作为中风后运动能力预测因子的重要性。

DESCRIPTION (provided by applicant): A primary impairment associated with post-stroke hemiparesis is the failure to make rapid graded adjustment of muscle force (i.e. muscle power) within the context of purposeful complex synergies (e.g., coordination during walking). Not surprisingly, the impact of stroke on walking is significant, with less than 50% of survivors progressing to independent community ambulation. Even among those who achieve independent ambulation, significant residual deficits persist in balance and gait speed, with ~75% of persons post-stroke reporting limitations in mobility related to walking. Muscle weakness is the most prominent motor consequence among the nearly 6 million survivors of stroke living in the United States and the strongest predictor of functional disability in this large clinical cohort. To date, the physiological mechanisms that contribute to muscle dysfunction in hemiparetic subjects are largely unstudied. Moreover, evidence regarding the efficacy of interventions aimed at attenuating impaired muscle function and the ensuing functional consequences in the post-stroke population is equivocal and viable therapeutic options to remediate hemiparetic muscle weakness remain among the most pressing challenges for biomedical research. We propose that impaired muscle power (the product of muscle strength and velocity) generation is causal of functional (walking) disability post-stroke. In addition, coordination deficits are also critical determinants of functional performance. We have developed a comprehensive theoretical framework that defines and measures the factors underlying disordered muscle function and coordination and will apply this framework to Post-stroke Optimization of Walking using Explosive Resistance (POWER) training. Our goals over the four year funding period are to 1) quantify neural and muscular adaptations that contribute to impaired muscle power generation post-stroke; 2) assess effects of POWER training on neural and muscular adaptations in paretic and non-paretic muscle; and 3) determine the relationship between changes in neural and muscular adaptations following POWER training and locomotor improvements. Innovative aspects of the proposed work include the novel training intervention; the advanced magnetic resonance assessments; as well as the unique measure of the coordination that we propose. It is our belief that: a) neural and muscular adaptations following stroke are associated with impaired muscle power generation as well as locomotor ability, b) POWER training attenuates functional deficits by addressing the underlying neural and muscular elements and c) functional improvements following training are predicated on improving the most prominent neural and muscular contributors to muscle power generation. If correct, the data generated will provide an entirely new level of evidence regarding the effectiveness of this novel intervention strategy on improving functional performance as well as the importance of peripheral muscle properties as predictors of locomotor ability post-stroke.